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Semaglutide as a Game Changer for Weight Loss

Mark A. Moyad, MD, MPH, the Jenkins/Pokempner Director of Preventive/Complementary and Alternative Medicine (CAM) at the University of Michigan Medical Center in the Department of Urology in Ann Arbor, Michigan, and Martin M. Miner, MD, Co-Director of the Men’s Health Center and Chief of Family and Community Medicine for Miriam Hospital, and Clinical Professor of Family Medicine and Urology at the Warren Alpert Medical School of Brown University in Providence, Rhode Island, discuss the potential benefits of semaglutide, a newly approved weight-loss drug. Dr. Moyad begins by summarizing the damage done by past weight-loss drugs, noting that they inevitably came with a huge catch and were never heart-healthy. He then introduces semaglutide, a recently-approved drug which has been shown to result in 15% weight loss over 2 years. Dr. Miner elaborates, explaining that there have been 4 studies of semaglutide featuring over 4500 individuals and that it is extremely safe. He highlights that the smaller dose in diabetics has also been shown to improve renal and cardiovascular outcomes, and that these outcomes are now being studied in non-diabetics. Dr. Miner argues that these results suggest semaglutide is a game changer. Dr. Moyad then discusses potential catches, noting that while the side effect profile seems good, the cost is very high at nearly $900 per month, and it is not covered by most insurance. Dr. Miner suggests that the price will go down once some time has passed from the initial approval. He does highlight as a negative the fact that semaglutide is given once per week as a subcutaneous injection, and suggests that it will be beneficial if the oral version currently under investigation is found to be effective. Drs. Miner and Moyad also ponder the long term impacts of semaglutide and sustained weight loss on testosterone levels, blood pressure, and depression. Dr. Moyad concludes by discussing his curiosity about the potential impact of semaglutide in a urologic setting.

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GU ASCO Symposium 2022 Summary

Ulka Vaishampayan, MD, Professor of Medicine and Genitourinary (GU) Oncology at the University of Michigan’s Rogel Cancer Center in Ann Arbor, Michigan, discusses highlights from the 2022 GU ASCO Symposium, focusing on advanced prostate cancer treatment research. She begins by discussing the phase 3 ARASENS trial, which looked at overall survival with darolutamide versus placebo in combination with androgen deprivation therapy (ADT) and docetaxel for metastatic hormone-sensitive prostate cancer (mHSPC). Dr. Vaishampayan explains that the investigators found that darolutamide significantly reduced the risk of death by 32.5%, and that this means that an overall survival benefit has now been seen with treatment intensification in 2 separate trials: PEACE-1 (docetaxel plus abiraterone) and ARASENS (docetaxel plus darolutamide). She argues that these results indicate that a triplet regimen with ADT, docetaxel, and darolutamide is the new standard of care in men with mHSPC. Dr. Vaishampayan then moves on to discuss the phase 3 PROpel trial of olaparib and abiraterone versus placebo and abiraterone as first-line therapy for patients with metastatic castration-resistant prostate cancer (mCRPC). She notes that PROpel found 34% risk reduction of progression or death with olaparib plus abiraterone, and that while overall survival data is fairly immature, the trend seems to favor olaparib plus abiraterone over placebo plus abiraterone. She also highlights that the safety profile of olaparib plus abiraterone was consistent with the safety profile for the individual drugs and there was no detriment to quality of life. Finally, Dr. Vaishampayan considers first results from the phase 3 MAGNITUDE study of niraparib with abiraterone acetate and prednisone as first-line therapy in patients with mCRPC with and without homologous recombination repair (HRR) gene alterations. She explains that MAGNITUDE showed a benefit to niraparib in the HRR arm, but no benefit in the non-HRR arm. Dr. Vaishampayan concludes that MAGNITUDE demonstrates the importance of testing for HRR gene alterations in patients with mCRPC to identify who will optimally benefit from the combination of niraparib and prednisone and also supports niraparib plus prednisone as a new first-line treatment option for patients with mCRPC and alterations in genes associated with HRR.

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Managing NMIBC in the BCG Shortage Era

Seth P. Lerner, MD, Professor of Urology and holder of the Beth and Dave Swalm Chair in Urologic Oncology in the Scott Department of Urology at Baylor College of Medicine, explains the bacillus Calmette-Guérin (BCG) shortage and discusses how physicians should adjust treatment decisions for non-muscle invasive bladder cancer (NMIBC). He outlines a joint guideline statement made by the AUA, AACU, BCAN, SUO, LUGPA, and UCF on February 19, 2019, which stated that BCG should not be used for low-risk disease, that alternative intravesical chemotherapy should be used for second-line intermediate-risk disease, that patients with high-risk NMIBC should be prioritized for full-strength BCG, and that if full doses are unavailable then reduced doses should be used. Dr. Lerner then discusses the SWOG BCG maintenance protocol, which shows a clear benefit over other protocols. He reviews the BCG dose reduction process and describes how to bill for it. Dr. Lerner also gives an overview of a trial on optimizing mitomycin delivery that found that dehydrating the patient and ensuring the bladder is empty prior to instillation is key, and that optimized delivery can double recurrence-free survival at 5 years. Dr. Lerner outlines BCG-naive clinical trial agents and shows data indicating that gemcitabine with docetaxel can be used to supplement BCG treatment. He states that very high-risk patients should receive radical cystectomies early due to a dropoff in survival in patients who wait to receive cystectomies. Dr. Lerner concludes that optimized intravesical mitomycin and doublet chemotherapy regimens are active in both intermediate and high-risk disease, and that radical cystectomy’s complete and usually durable response for pathologic NMIBC should not be ignored.

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The Myths and Facts About Prostate Brachytherapy

As part of a special course on brachytherapy for prostate cancer from the American Brachytherapy Society and Grand Rounds in Urology, Steven J. Frank, MD, Professor of Radiation Oncology at the University of Texas MD Anderson Cancer Center, Medical Director of the Proton Therapy Center at MD Anderson, and leader of both the Proton Therapy Program for Head and Neck Cancer and the Prostate Brachytherapy Program, introduces the many myths about brachytherapy and dispels them with data, revealing the truth of brachytherapy and its effects. He shows data asserting that patients under 60 and obese patients are great candidates for brachytherapy. Dr. Frank then discusses how radiation exposure to a patient’s family is less than what a flight from New York City to San Francisco would cause, and that brachytherapy has great curative ability based on a PSA of .2 ng/ml at 4 years being curative. He describes how long-term data and outcomes for brachytherapy are in the treatment’s favor, showing that it is an excellent option for low-, intermediate-, and high-risk cancer. Dr. Frank states that patient satisfaction is greater with brachytherapy than other treatments due to low rates of urinary incontinence and reduction in sexual function, and no penile shortening or treatment regret. He summarizes how salvage therapy and salvage brachytherapy following radiation have been found to be effective but require skilled and experienced teams. Dr. Frank also discusses asymptomatic seed migration 3 years after implantation, the lack of data on hair loss, the safety of cremation, and how MRI-assisted radiosurgery is an innovation in brachytherapy. He concludes that brachytherapy has been found to be the most innovative, cost-effective, satisfying, and curative prostate cancer treatment.

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Point-Counterpoint: Management of mCRPC

Rana R. McKay, MD, Associate Professor of Medicine at the University of California, San Diego, and Co-Leader of the Genitourinary Oncology Disease Team at the Moores Cancer Center, and Alan H. Bryce, MD, Medical Director of the Genomic Oncology Clinic at Mayo Clinic Arizona in Scottsdale, debate whether to treat metastatic castration-resistant prostate cancer (mCRPC).

Taking the pro position, Dr. McKay presents on why physicians need to treat mCRPC, as well as come up with additional treatment options to help improve survival for mCRPC patients. She discusses the goals of mCRPC treatment, improved quality of life and overall survival, and displays a chart that summarizes the current landscape of treatment for advanced prostate cancer as she details how androgen receptor (AR) targeting agents are enhancing treatment. Dr. McKay reviews FDA-approved agents in mCRPC, stating that the vast majority both improve overall survival and quality of life. She specifically states that the agents, outside of pembrolizumab, rucaparib, and sipuleucel-T, can potentially increase overall survival by 53.6 months and improve cancer-associated pain, disease-related urinary symptoms, and symptomatic skeletal events. Dr. McKay then shows a graph displaying mCRPC treatment in a clinical practice, suggesting that mCRPC is grossly undertreated based on the vast majority of patients not going beyond first-line treatment. She states that there is little reliable data on the cost effectiveness of treatment and concludes that mCRPC should be treated based on data showing that treatments improve overall survival and quality of life.

Taking the con position, Dr. Bryce makes an argument against treating mCRPC based on the differences between trial and real-world populations, and the challenges of extreme treatments. Dr. Bryce cites quality of life post-treatment, financial toxicity, and patient-centric treatment as cons of mCRPC treatment. He shows a graph of mCRPC treatment management in clinical practice and states that the rapid drop off after first-line therapy could be caused by patient drop outs instead of undertreatment. Dr. Bryce discusses the mCRPC treatment process in detail, focusing on how after the first line of therapy, treatment options become much more extreme and mostly consist of chemo, and most patients only have about a year left to live if they are beyond second-line treatment. He uses a case study of a 73-year-old patient to show how real-world patients can differ from selected trial patients due to how patient selection leads to optimized outcomes. Dr. Bryce reviews data showing that 20% of patients report financial toxicity, something which is associated with anxiety and depression. He concludes that clinicians should exercise prudent judgment in deciding whether or not to treat patients with advanced cancer due to trials testing beyond third-line therapy not reflecting real-world patients and financial toxicity being a significant issue.

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